I've been to SA twice (my ex was S. African). I never went on a safari, but we had planned on it. I was told the only thing you needed was malaria medication (for prevention), but that that makes you sick. That was in 2000, so I think they have found a medicine that makes you less sick.

I've been to Jo'burg, stayed in Pretoria and drove across to Cape Town. I then stayed again in Cape Town. I think for the best safari, you would have to go to Kruger, which is about a few hours from Jo'burg.

Talk to your doctor. Personally, I would do it if I were in your situation. SA isn't as bad as the rest of Africa and if you stick to major cities or close by and are with people who are from there, it can't be that bad. I wouldn't suggest it if you weren't with someone who knows the country; it is unsafe of you ask me.